Interpretive Summary: Epidemiological studies have indicated that maternal under nutrition such as low protein diet increases offspring’s susceptibility to obesity in adulthood. Many studies also showed that maternal low protein diet causes heritable changes in the offspring’s fat tissue. These heritable changes have been shown to occur during pregnancy and especially if offspring are exposed to a high fat diet after birth so that offspring’s fat cell size and numbers as well as how fat cells store and utilize energy is dysregulated. Therefore, we fed obese prone female rats with diets of 8% (low protein, LP) or 20% (normal protein, NP) protein for 3-wk prior to conception and throughout pregnancy and lactation and fed male offspring with 10% (normal fat, NF) or 45% (high fat, HF) fat diets for 12 weeks after weaning. Our hypothesis was that offspring exposed to maternal LP and postnatal HF diet have increases in fat cell size and numbers, fat tissue growth rates, and expression of fat tissue growth hormone insulin like growth factor 2 (IGF-2) gene. Additionally, we hypothesized that number and function of fat cell mitochondria, well known to regulator energy balance and energy utilization, is decreased in the fat cells because of prenatal LP and postnatal HF diets. Our data showed significant increases in adipose tissue growth rate, IGF-2 gene expression, and numbers of fat cells while mitochondria numbers and energy utilizing functions were significantly decreased in the offsprings that were exposed to LP prenatal diet and fed HF postnatal diets. These findings suggest that prenatal dietary protein and postnatal high fat intake levels influence the rate of adipose tissue growth and growth hormone gene expression levels. These data also demonstrate that increased adipose tissue growth may be due to decreased fat cell energy utilization caused by decreased mitochondria numbers and mitochondrial energy utilizations.

Technical Abstract:
Maternal low protein diets during prenatal development contribute to the development of obesity and insulin resistance in offspring. In this study, obese-prone Sprague -Dawley rats were fed diets having either 8% (low protein, LP) or 20% (normal protein, NP) protein for 3-wk prior to conception and throughout pregnancy and lactation. At weaning, their offspring were fed diets for 12 wk having normal protein and either 10% (normal fat, NF) or 45% (high fat, HF) fat. Adipose tissue growth rate was increased by HF postnatal diet, but the rate was greater in the offspring of LP-fed dams (26-fold increase) compared to NP-fed dams (13-fold increase). IGF2 mRNA was increased by HF postnatal diet in subcutaneous, but not in visceral, adipose tissue regardless of the dams’ prenatal diet. The HF postnatal diet increased the number of small adipocytes (20-80 µm, P<0.005) in visceral adipose tissue of offspring regardless of their dams’ prenatal diet, but the increase in smaller adipocytes did not occur in the subcutaneous adipose tissue of offspring fed HF diet whose dams were fed LP prenatal diet. Mitochondrial DNA copy number was lower in subcutaneous adipose tissue of offspring fed HF diet if their dams had been fed the LP diet. Neither prenatal protein intake nor postnatal fat intake influenced mitochondrial copy number in visceral adipose tissue. These findings suggest that prenatal dietary protein intake influences the rate of adipose tissue growth in offspring in response to high fat intake through alterations in adipocyte numbers and sizes. The mechanism may involve depot specific effects of prenatal protein intake on the expression of the epigenetically imprinted Igf2 gene and energy utilization during preadipocyte differentiation.